cortodoxone and Neoplasm-Metastasis

Megestrol acetate (MA) is of therapeutic value in breast cancer patients. This study was designed to evaluate the effects of different dosages of MA on endocrine events potentially influenced by the drug in relation to plasma level of MA and clinical effects in patients with advanced breast cancer. Eighteen postmenopausal patients were randomly distributed over six groups to receive daily 90, 180 or 270 mg of MA (niagestin) orally in a cross-over study consisting of 3 periods of 6 weeks. Complete remission was observed in 1 patient, partial remission in 9, no change in 4 and failure in 4 patients. During the 18 weeks of treatment plasma levels of MA gradually increased, irrespective of the dose administered. Significant rises of the basal and TRH-stimulated plasma PRL and basal insulin levels were observed, whereas LH and FSH, estradiol, SHBG and the pituitary-adrenal axis were suppressed. None of these metabolic effects showed a correlation with the clinical response. We concluded that treatment of metastatic breast cancer with 180 mg MA/day is effective and causes minimal adverse effects.

Topics: Administration, Oral; Aged; Blood Glucose; Breast Neoplasms; Cortodoxone; Drug Administration Schedule; Estradiol; Female; Humans; Insulin; Megestrol; Megestrol Acetate; Middle Aged; Neoplasm Metastasis; Pituitary Hormones, Anterior; Sex Hormone-Binding Globulin

Adrenocortical carcinoma is a rare malignancy in children, with a high mortality. Little is known about long-term outcome, especially in infants treated with mitotane. We report the successful long-term outcome of a case of metastatic adrenocortical carcinoma presenting in infancy treated with surgical resection and mitotane. The patient presented at 2 months of age with Cushing's syndrome, a large adrenal mass, and elevated adrenal steroid levels. The tumor was removed surgically. Intraoperative findings included an adrenal tumor (confirmed malignant pathologically) invading the adrenal vein and vena cava. After surgery he was treated with mitotane at a dose of 2 g/d. Six months after surgery 11-deoxycortisol levels increased, and a computed tomography scan showed a pulmonary metastasis. Mitotane was increased to 2.5 g/d, and the metastasis was removed surgically. Plasma mitotane levels ranged 10-15 micro g/ml. Tumor markers remained normal, and mitotane was discontinued at 18 months. During therapy the patient's somatic growth was poor. His motor and speech development was delayed. After mitotane was discontinued he demonstrated catch-up growth. This case shows successful long-term outcome and recovery from the toxic effects of mitotane.

Topics: Adrenal Cortex Neoplasms; Antineoplastic Agents, Hormonal; Carcinoma; Cortodoxone; Growth Disorders; Humans; Infant; Lung Neoplasms; Male; Mitotane; Neoplasm Metastasis; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography

We present nine cases of primary adrenocortical carcinoma, collected in our department of medicine and endocrinology over 25 years. In our patients, the most dependable tumor marker was urinary excretion of tetra-hydro-ll-deoxycortisol (THS), and elevated values were found in all cases where it was determined. In addition to surgical treatment, medication with o,p'-DDD was found to be of value for some of the patients. Median tumor weight was 487 g (118-2,085 g). Prognosis is difficult to predict. Median survival time after diagnosis was 34 months, but varied from three to 266 months.

Topics: 17-Ketosteroids; Adrenal Cortex Neoplasms; Adult; Aged; Biomarkers, Tumor; Cortodoxone; Cushing Syndrome; Female; Humans; Hydrocortisone; Male; Middle Aged; Mitotane; Neoplasm Metastasis; Prognosis

The effect of angiostatic steroids on pulmonary metastasis was investigated using mice treated with such a steroid before or after intravenous inoculation with Lewis lung carcinoma; cortisone acetate and tetrahydro S, of which the former possesses glucocorticoid activity, and the latter lacks it, were used as the angiostatic steroids. In the presence of heparin, both types of steroids prevented angiogenesis in chick embryo and also pulmonary metastasis in mice when the administration started after cell lodgement. On the other hand, one-shot cortisone treatment before cell inoculation increased the weight of lung colonies to twice that seen in the controls, while tetrahydro S pretreatment did not enhance metastasis. These results revealed that both angiostatic steroids with and without glucocorticoid activity in the presence of heparin inhibited tumor growth in the lungs, and further indicated that cortisone acetate affected the steps of metastasis after the invasion of tumor cells into the blood stream until angiogenesis in the secondary foci, and consequently promoted metastasis, whereas tetrahydro S (which has no glucocorticoid activity) did not affect the steps before angiogenesis. It was thus indicated that the inhibitory effect of angiostatic steroids against tumor growth due to an anti-angiogenic activity was not dependent at all on the metastasis promotion by these steroids having glucocorticoid activity.

Topics: Allantois; Animals; Chick Embryo; Cortisone; Cortodoxone; Glucocorticoids; Heparin; Lung Neoplasms; Male; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Neovascularization, Pathologic; Structure-Activity Relationship